The protective function of skin and hence its low permeability presents a formidable obstacle in therapeutical applications such as transdermal drug delivery and gene delivery in skin. One of the methods to temporarily increase skin permeability is electroporation, creating aqueous pathways across lipid-based structures by means of electric pulses. Also, the application of electric pulses to biological cells causes increased permeability of cell membrane, thus enabling the uptake of larger molecules that otherwise cannot cross the membrane, such as drug molecules or DNA, into the cell. The creation of localized sites of increased molecular transport termed local transport regions (LTRs) can be observed during electroporation, as well as changes in the bulk electric properties of skin layers. We modeled these phenomena with a numerical model and compared the output of the model with our own in vivo experiments and previously published results of skin electroporation and a good agreement was obtained. With the model presented, we used the available data to describe the nonlinear process of skin electropermeabilization from the aspect of tissue conductivity changes and the presence of local transport regions in the permeabilized stratum corneum. The observations derived from various in vivo experiments by different authors were thus confirmed theoretically.